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首页> 外文期刊>Infection and immunity >Isotype Switching Increases Efficacy of Antibody Protection against Cryptococcus neoformans Infection in Mice
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Isotype Switching Increases Efficacy of Antibody Protection against Cryptococcus neoformans Infection in Mice

机译：同种型切换增加了抗小鼠新型隐球菌感染的抗体保护的功效。

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The isotype and epitope specificities of antibodies both contribute to the efficacy of antibodies that mediate immunity toCryptococcus neoformans, but the relationship between these properties is only partially understood. In this study, we analyzed the efficacy of protection of two sets of immunoglobulin G (IgG) isotype switch variants from two IgG3 monoclonal antibodies (MAbs) which are either not protective or disease enhancing, depending on the mouse model used. The two IgG3 MAbs 3E5 and 4H3 have different epitope specificities. Protection experiments were done with A/JCr mice infected intravenously with C. neoformans and administered with 3E5 IgG3 and its IgG1, IgG2a, and IgG2b switch variants. These experiments revealed that IgG1, IgG2b, and IgG2a were each more effective than IgG3. For 4H3 IgG3 and its IgG1 and IgG2b switch variants, the relative efficacy was IgG2b > IgG1 IgG3. The combination of 3E5 IgG3 and 4H3 IgG3 was more deleterious than either IgG3 alone. All IgG isotypes were opsonic for mouse bronchoalveolar cells, with the relative efficacy being IgG2b > IgG2a > IgG1 > IgG3. These results (i) confirm that a nonprotective IgG3 MAb can be converted to a protective MAb by isotype switching, (ii) indicate that the efficacy of protection of an IgG1 MAb can be increased by isotype switching to another subclass, (iii) show that protective and nonprotective IgG MAbs are opsonic, and (iv) provide additional evidence for the concept that the efficacy of the antibody response to C. neoformans is dependent on the type of MAb elicited.
机译：抗体的同种型和表位特异性均有助于介导对新型隐球菌免疫的抗体的功效，但这些性质之间的关系仅得到部分了解。在这项研究中，我们分析了保护两种小鼠免疫球蛋白G（IgG）同种型开关变体来自两种IgG3单克隆抗体（MAb）的功效，这些变体既不是保护性的也不是疾病增强型，具体取决于所用的小鼠模型。两种IgG3 MAb 3E5和4H3具有不同的表位特异性。用静脉注射 C的A / JCr小鼠进行保护实验。并施用3E5 IgG3及其IgG1，IgG2a和IgG2b开关变体。这些实验表明，IgG1，IgG2b和IgG2a均比IgG3更有效。对于4H3 IgG3及其IgG1和IgG2b开关变体，相对功效为IgG2b> IgG1 IgG3。 3E5 IgG3和4H3 IgG3的组合比单独的IgG3更具有害性。对于小鼠支气管肺泡细胞，所有IgG同种型都是调理的，相对效力为IgG2b> IgG2a> IgG1> IgG3。这些结果（i）证实可以通过同种型转换将非保护性IgG3 MAb转化为保护性MAb，（ii）表明通过同种型转换为另一亚类可以提高IgG1 MAb的保护功效，（iii）表明保护性和非保护性IgG MAb是调理性的，并且（iv）为抗体对 C反应的功效这一概念提供了更多证据。新甲虫取决于引出的单克隆抗体的类型。

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